This invention relates generally to the separation or filtration of blood components, and more particularly concerns improvements in method and apparatus employing permeable membranes to achieve such separation.
When membranes are employed to filter blood, i.e. to separate liquid such as plasma from particulate, as for example, red blood cells, or platelets, it is found that the flow through membrane openings tends rapidly to reduce over time, such openings initially being sized to block passage of the particulate, to provide filtering. Efforts to prevent such flow reduction due to clogging of the membrane have included increasing the membrane area, the shear rate of the flowing blood, and/or the pressure differential across the membrane so as to delay the clogging effect or to drive the fluid component of the blood through partially clogged perforations.
Viscous shear conditions in the blood flowing over a membrane create dynamic forces opposing particulate flow toward the perforations or holes through the membrane; however, flow toward and through the holes tends to drag particulate toward and into the openings. At the so called critical filtration velocity, such dynamic forces and the opposing drag forces are in balance, whereby particles are not displaced toward or away from the holes; at filtration velocities higher than critical, the red cells tend to approach the perforations essentially piling up on the membrane ("polarization"), and at filtration velocities lower than critical, the red cells or subject particulates tend to remain spaced from the membrane. The critical filtration velocity is different for different size particles, increasing approximately as the square of particle diameter. Above the critical filtration velocity and in the polarized condition wherein blood cells form a concentrated layer over the membrane surface the flow of filtrate, i.e., plasma is substantially reduced for two reasons. The most apparent one is that plasma must flow past a dense matrix of cells in order to reach the membrane. The second, less obvious, reason is that the maintenance of uncontaminated plasma flow becomes exquisitely sensitive to transmembrane pressure (TMP). If TMP exceeds a very low threshold, usually only 50 to 100 mm Hg. the blood cells overlying the membrane pores will be deformed and forced into and extruded through the pores causing undesirable blood cell damage (hemolysis) and accelerated plugging of the pores. Consequently, the obligatory low TMP fundamentally limits the flow of plasma through the membrane.
Even below the critical filtration velocity and despite higher permissible differential pressures across the membrane in the absence of polarization, pore openings, sized to hold back the blood cells or retain particulates in general, tend to become clogged due either to protein interaction with the membrane, e.g., coating, or simply swelling of the membrane substrate, thus, progressively reducing filtering efficiency and filtrate production. In this regard, filtration velocity refers to average flow rate per unit portion of membrane area rather than actual velocity within a pore. Clearly, there is need for material and means to prevent or reduce the membrane hole or pore clogging tendency.